We are studying the fusion of phospholipid vesicles with planar, phospholipid bilayer membranes. We use two criteria for successful fusion: (1) The incorporation into the planar membrane of a protein originally present in the vesicular membrane, and (2) the transfer of vesicular contents across the planar membrane. Fusion is obtained when the compartment containing the vesicles (the cis compartment) is hyperosmotic with respect to the opposite one. The fusion rate is stimulated by millimolar amounts of divalent cation (Mg ions, Ca ions, Ba ions in the cis compartment. When a calcium-binding protein obtained from synaptic membranes is present in the planar membrane, the fusion rate is stimulated by micromolar amounts specifically of Ca ions. We believe that the same mechanism of fusion that occurs in the model system also operates in biological exocytosis, such as transmitter release at synapses.